This invention relates to compositions and methods for normalizing impaired or deteriorating neurological function in humans. More particularly, this invention relates to compositions and methods which use a holistic approach for normalizing impaired or deteriorating neurological function in humans.
For various reasons, approximately 20-50% of all the populations of global cultures experience varying types and degrees of nervous system deterioration and/or dysfunction.
Impaired or deteriorating neurological functions are manifested by a variety of conditions spanning a spectrum of states of nervous system dysfunction. Non-limiting examples of such conditions include memory deterioration, certain behavioral problems, attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), other inattention and/or hyperactivity syndromes, dementia or cognitive decline of multiple etiologies, various genetic disorders (e.g., Downs Syndrome, Fragile X Syndrome, etc.), central nervous system (CNS) trauma, intoxications (acute and chronic) or poisoning, auto-immune mechanisms, anoxic-ischemic conditions, neurodegenerative disorders, metabolic afflictions of the nervous system, vascular insults, hypertensive encephalopathy, rheological disorders, demyelination, cerebral edema, inflammatory neuronal conditions, learning disabilities, impulsive behavior, specific emotional or mood problems, difficulty functioning under pressure, various latrogenic conditions, infections, eleptogenic foci and congenital brain malformations.
Methods and compositions for treating neurological dysfunction are known in the art.
U.S. Pat. No. 6,020,139 to Schwartz et al. is directed to methods for identifying a therapeutic composition or protocol which ameliorates a disease or undesired condition in a subject, wherein the methods rely upon recognition of the existence of and interconnections between eight S-adenosyl-L-methionine (SAM) pathways. The methods involve determining the presence of the disease or condition in a subject; identifying any abnormalities in each of the eight SAM pathways by determining concentrations of metabolites and/or concentrations or activities of enzymes and/or levels of cellular functions, that are participants in or are results of SAM pathways, thereby obtaining a data set of the differences of the concentrations, activities and/or levels from corresponding normal concentrations, activities and/or levels; analyzing the data set in such a way as to determine which of the metabolites, enzymes and/or cellular functions of the SAM pathways is a causative agent of the differences in concentrations, activities or levels; and identifying a therapeutic composition or protocol which acts to restore the pathways toward normality so as to ameliorate the disease or condition. Diseases or conditions which the methods are designed to treat include Alzheimer's disease, Parkinson's disease, and atherosclerosis. The therapeutic composition used in the invention may be composed of a SAM metabolite or an agent that influences the activity of a SAM pathway or a pathway that is modulated by a SAM pathway. The patent lists compounds the presence and levels of which should be measured and/or monitored in various diseases. For example, for Alzheimer's disease, metabolites, enzyme activities and/or cellular functions which should be monitored include one or more methylation levels, SAM, biotin, polyamines, folate, and vitamin B2. For Parkinson's disease, the metabolites or enzyme activities include polyamines, non-specific N-methylase, acetyl-L-carnitine, Ca2+/calmodulin-dependent protein kinase II, lysolecithin, sphingomyelin, SAM and vitamin B12. For atherosclerosis, the metabolites, enzyme activities, or cellular functions involve methylation levels, polyamines, acetyl-L-carnitine, calmodulin, and essential phospholipids.
U.S. Pat. No. 5,668,117 to Shapiro discloses a method and composition for treating neurological diseases, wherein the composition contains at least one carbonyl trapping agent alone or in combination with a co-agent or medicament. According to the Shapiro patent, the method and composition can be used to treat, e.g., Alzheimer's disease, Parkinson's disease, hereditary motor and sensory neuropathies, age-onset neurological deterioration, multiple sclerosis, diabetic polyneuropathy, Down's Syndrome, olivopontocerebellar atrophy, amyotrophic lateral sclerosis, alcoholic polyneuropathy, and tinnitus (nerve deafness). According to the patent, co-agents which can be used in the treatment of Parkinson's disease include, e.g., carbidopa and levodopa compositions, dopamine agonists, anticholinergic medications, antihistamines, tricyclic antidepressants, serotonin reuptake inhibitor antidepressants, beta blocker agents, selegiline, D-cycloserine, neurotransmission enhancer drugs, peripheral decarboxylase inhibitors other than carbidopa, N-methyl-D-aspartate glutamate receptor antagonists, tacrine, 9-amino-1,2,3,4-tetrahydroacridin-1-ol, lazabemide, tiapride, and antioxidant agents. The patent teaches that co-agents useful in treating Alzheimer's disease include vasodilator or other nootropic direct brain metabolic enhancer drugs (e.g., idebenone, vinpocetine, and the like), neurotransmission enhancer drugs, tiapride, psychotherapeutic drugs, acetylcholinesterase inhibitors (e.g., huperzine A), calcium channel blocker agents, biogenic amines, antirage drugs, minor tranquilizers, angiotensin-converting enzyme inhibitors, agents which may enhance acetylcholine synthesis, storage or release (e.g., phosphatidylcholine), postsynaptic receptor agonists, ganglioside, specific monoamine oxidase-A inhibitors, N-methyl-D-aspartate glutamate receptor antagonists, nonsteroidal anti-inflammatory agents, selegiline, thiamine, anfacine, sulbutiamine, antioxidant agents, specific monoamine oxidase-B inhibitors, linopirdine, D-cycloserine, and serotonergic receptor antagonists. The Shapiro patent also discusses the use of para-aminobenzoic acid, DL-methionine, vitamin E, panthotenic acid, beta-carotene, selenium, vitamin B1 and a tablet containing folic acid, vitamin B2, vitamin B6, biotin, vitamin B1, niacin, Vitamin B12 and panthotenic acid, to treat a human suffering from hereditary motor and sensory neuropathy.
U.S. Pat. No. 4,812,447 to Roberts discloses a method for treating nervous system deterioration associated with aging and Alzheimer's disease, involving administering a therapeutically effective amount of dehydroepiandrosterone (DHEA) or its sulfate and, optionally, a potassium channel antagonist. The Roberts patent is further directed to pharmaceutical compositions containing DHEA, alone or in combination with a potassium channel antagonist, e.g., 4-aminopyridine. The patent teaches that DHEA facilitates the growth of nervous system tissue.
U.S. Pat. No. 5,104,880 to Kozikowski discloses the use of huperzine A analogs as acetylcholinesterase inhibitors which may be useful for treating memory and learning disorders such as, e.g., Alzheimer's disease, myasthenia gravis, and other age-related memory impairments.
U.S. Pat. No. 5,716,614 to Katz et al. discloses a pharmaceutical composition for treating diseases relating to severe deterioration of the central nervous system (e.g., dementias, neurodegenerative disorders, neurological diseases, malignant brain tumors, and inborn errors of metabolism), wherein the composition contains a complex of a polycationic carrier (e.g., poly-lysine, poly-arginine, or poly-ornithine) coupled to eicosapentaenoic acid or docosahexaenoic acid moities, a biologically active agent and one or more additional docosahexaenoic acid moieties. The one or more additional docosahexaenoic acid moieties are selected from docosahexaenoic acid-containing phosphatidyl serine, docosahexaenoic acid-containing phosphatidyl ethanolamine, and phosphatidyl carnitine.
Japanese Patent JP401221316A discloses a cerebral circulatory metabolism-improving agent composed of idebenone and vinpocetine.
Japanese Patent JP410053526A discloses a composition for treating, among other things, nervous symptoms caused by Alzheimer's disease, wherein the composition contains a vitamin B1 derivative or its salt and idebenone.
U.S. Pat. No. 6,063,820 to Cavazza is directed to a medical food for diabetics which includes linolenic acid, alkanoyl-L-carnitine, and, optionally, coenzyme A, antioxidants (e.g., lipoic acid, resveratrol, glutathione, selenium, and the like), taurine, pantethine, vitamin A, vitamin E, vitamin B1, vitamin B6, vitamin B12, magnesium, calcium, zinc, selenium, chromium, and vanadium. The patent teaches that peripheral neuropathies of the autonomic nervous system may be among the late complications of disease.
U.S. Pat. No. 6,117,872 to Maxwell et al. discloses a composition for enhancing exercise performance by augmenting endogenous nitric oxide production or activity, the composition containing L-arginine, L-lysine, and, optionally, antioxidants (e.g., vitamins A, C and E, cysteine, glutathione), or other factors which may enhance endothelial-derived nitric oxide (EDNO) synthesis or activity, such as folic acid, biopterins, B complex vitamins (specifically, B6 and B12), flavonoids (e.g., resveratrol), carotenoids (e.g., lycopene, phytoestrogens), L-carnitine, L-creatine, and L-taurine.
Current sophisticated investigative techniques have facilitated ever greater insight into the subtle abnormalities responsible for the diverse neurological conditions mentioned previously herein. As knowledge of these complex mechanistic pathways of disease has accumulated, many potential sites have become available for possible therapeutic intervention. The basic pathways which either individually or collectively are responsible for neurological deterioration or dysfunction may generally be classified as follows:                1) bioenergetics or the intrinsic ability of individual neurons or neural networks to generate and/or utilize an adequate, continuous supply of readily usable fuel to power the ongoing needs of every individual cell under steady state as well as adverse conditions;        2) nitrogenous and/or oxidative stress;        3) apoptosis;        4) maintenance of cellular and subcellular membrane structure and function, fluidity, permeability characteristics, receptor and channel activity, and signal transducing capability;        5) neurochemistry and neurotransmission;        6) vascular wall integrity and function;        7) neurotransmission;        8) protection of nuclear and mitochondrial DNA;        9) maintenance of neuronal plasticity;        10) inflammation;        11) nerve growth factors;        12) metal ionic effects;        13) aberrant methyl metabolism;        14) cortisol (glucocorticoid) activity;        15) insulin action; and        16) stress protein activity.        